The roles of fibrinogen and fibronectin were contasted in the responses of human platelets to Staphylococcus aureus and collagen. Congenital afibrinogenemic (CA) platelets and washed normal platelets had delayed aggregation due to a prolonged latent phase in response to contact with the bacteria when fibrinogen was absent from the suspending media. When a physiologic level of human fibrinogen was added to the CA platelets in autologous plasma or to the washed platelets in balanced saline, the times to aggregation were significantly shortened (P < 0.05) and restored to rates comparable to those of normal platelets in whole plasma. In contrast, the presence or absence of fibrinogen in the media had no significant effect on the initial adherence and shape‐change response of CA or washed platelets to collagen. Platelets with a demonstrated aberration of fibronectin responded normally to all ratios of S aureus, but they responded only to doses of collagen that were several times the threshold levels for normal platelets. These results demonstrate an important role for fibrinogen as a cofactor in platelet interactions with S aureus and indicate that fibronectin is not a major factor in the responses of human platelets to this microorganism.